2-Keto-4-hydroxyglutarate is an important and novel enzyme involved in the catabolism of L-hydroxyproline by mammals. Using this enzyme as obtained in pure form from extracts of bovine kidney, bovine liver, and E. coli K-12, we have research in progress and shall continue our studies relating to the molecular and catalytic properties of this aldolase, the functional groups which participate in the catalytic process, the isolation of active-site peptides, and the establishment of structure-function relationships in general. Comparative enzymology is done. Having established that 2-keto-4-hydroxyglutarate is a substrate for the well-known alpha-ketoglutarate dehydrogenase complex of the TCA-cycle, efforts are being made to establish the metabolic role in procaryotes of both aldolase and dehydrogenase activity toward 2-keto-4-hydroxyglutarate. In addition, the properties and function of L-threonine dehydrogenase (one of three enzymes that initiate threonine degradation in eucaryotes and procaryotes) and also D-1-amino-2-propanol:NAD ion oxidoreductase are being studied.